All fibrinogen (FBG)-bearing proteins documented to date in the freshwater snail Biomphalaria glabrata, the intermediate host of the human blood fluke Schistosoma mansoni, possess the same molecular structure; one or two immunoglobin superfamily (IgSF) domains at the N-terminus and a FBG domain at the C-terminus (named as FBG-related protein (FREP)). Here we report two novel genes that encode FBG-bearing proteins from B. glabrata. Different from all known FREPs, the first gene encodes a protein (657 amino acids (aa)) composed of a long N-terminal region with no sequence homology to any known protein, a middle epidermal growth factor (EGF) repeat region and a C-terminal FBG domain, designated FBG-related molecule (FReM). Differential expression at 2 days post-exposure (dpe) to the trematode S. mansoni or Echinostoma paraensei was found in the S. mansoni susceptible M line and resistant BS-90 snail strains. The second gene is a new member of the FREP family, designated FREP14, which encodes a 399 aa putative secreted protein. FREP14 is different from known FREPs in that it is encoded by a single locus and is not upregulated in early or late stage S. mansoni exposure, but is upregulated in late stage E. paraensei infection. Furthermore, gene expression during the snail's ontogenesis and at a late stage of trematode infection (52 dpe) has been investigated in the two newly identified genes (FReM and FREP14) described in this paper and five representative members of known FREPs (FREPs 2, 3, 4, 12, and 13). A variety of expression patterns were observed, suggestive of functional diversity among the members of FBG-bearing proteins. Our findings further broaden our understanding of the diversity and function of the FBG-bearing protein encoded genes in B. glabrata.